The goal of this proposal is to facilitate the candidate's transition to a role as a leading academic researcher and multidisciplinary team member developing optical fluorescence-based technology, with the goal of improving extent of tumor resection (EOTR) in brain cancer. In particular, a focus of this proposal is on advancing fluorescence-guided surgery (FGS) within the context of neurosurgical oncology. To this end, the proposal outlines a mentored-training program with a strong clinical emphasis to compliment the candidate's proficiency in medical and optical imaging, placing the candidate within a critical mass of NIH-funded researchers at Dartmouth Hitchcock Medical Center (DHMC). The plan will focus on four complimentary areas: 1) providing a solid understanding of neurosurgical oncology, 2) developing an expertise in cancer molecular biology, 3) leading a pre-clinical investigation of molecular-guided cancer surgery, 4) expanding skills in optical engineering and machine learning, all of which will emphasize the synergy between understanding the clinical problems in neuro-oncology and advancing technology to address these problems. These goals are strongly supported by an experienced mentor team, led by neurosurgery section-chief Dr. Roberts, alongside NIH-funded researchers Profs. Paulsen, Pogue, and Hoopes. Leveraging the extensive opportunities at Dartmouth, the candidate will use K99 funding to devote time to graduate courses in cancer biology, medical imaging, and translational medicine, and to attend cancer workshops, training seminars, and CME-accredited Grand Rounds at the NCI Norris Cotton Cancer Center. The candidate will also attend AACR workshops to further strengthen clinical understanding of neuro-oncology, and provide a venue for presentation and feedback on the research work. The firm knowledge base gained by this training plan will be applied within the context of a pre-clinical research project to develop and evaluate a novel method of FGS- molecular-guided surgery (MGS) by means of intraoperative receptor concentration imaging (iRCI). The project will extend the rapidly growing field of FGS, applying a novel kinetic imaging approach to allow intraoperative evaluation of tumor-associated receptor expression, and to use this to guide surgical resection. Aim (1) will be to develop and test iRCI in a rat model of GBM, evaluating the accuracy of MGS to identify positive tissue and to improve EOTR compared with current FGS methods. Aim (2) will be to advance the current FGS camera systems, incorporating arterial input function measurement, and reducing absorption and scatter-based artifacts due to surface blood at the surgical site. Aim (3) will be to facilitate iRCI integrationinto the surgical workflow through strategic improvements in dye administration and AIF characterization. This proposal will expand the candidate's knowledge-base in cancer biology and surgical oncology, through extensive training opportunities and interactions with a strong multi-disciplinary team of mentors, equipping the candidate with all the necessary skills to accelerate the trajectory of his promising research career.